The Effect of Prophylactic TPO Combined With BMS-IMRT to Esophageal Cancer Patients

July 12, 2023 updated by: JIANYANG WANG

A Prospective Phase II Study of Prophylactic TPO Combined With Bone Marrow-Sparing Intensity-Modulated Radiotherapy to Reduce Platelet Inhibition in Patients With Esophageal Cancer Undergoing Concurrent Chemoradiotherapy

The goal of this interventional study is to explore the protective effect of prophylactic TPO combined with bone marrow sparing (BMS)-IMRT in patients with esophageal cancer undergoing concurrent chemoradiotherapy. The main purpose is to reduce the incidence of all grades of thrombocytopenia from 35% to less than 10% by the intervention of study.

Participants will initiate concurrent chemoradiotherapy within 2 weeks after enrollment,and they will receive subcutaneous injection of recombinant human thrombopoietin (rhTPO) 15000U once a week during the radiotherapy.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Concurrent chemoradiotherapy (CRT) is one of the standard treatments to the patients who initiate neoadjuvant chemoradiotherapy or radical radiotherapy. Previous large phase III trials of preoperative concurrent chemoradiotherapy and definitive chemoradiotherapy (Dt 40-60Gy) in esophageal cancer have shown rates of platelet inhibition (grade 1-4) of 25-54%. Concurrent chemotherapy has been associated with a significant increase in acute hematologic toxicity (HT) associated with radiation therapy, increasing the risk of infections, blood transfusions, colony-stimulating factors, and length of hospital stay. More importantly, severe myelosuppression also delays or interrupts the delivery of chemotherapy and radiotherapy, potentially reducing efficacy. In addition, the efficacy of locally advanced patients is still not optimistic, and the intensity of treatment may need to be increased. Therefore, if hematologic toxicity can be reduced, it may lead to more intensive concurrent chemoradiotherapy in the hope of further improving the efficacy.

Intensity-modulated radiation therapy (IMRT) has an absolute advantage over conventional radiotherapy in increasing the dose to the target volume and reducing the dose to normal tissues. Previous studies have shown a significant association between the volume of 10Gy (V10) and the volume received 20Gy (V20) of the pelvic and lumbosacral bone marrow and the development of acute HT when pelvic tumors are treated with IMRT. Thus, reducing the volume of bone marrow receiving low-dose radiotherapy may reduce the occurrence and severity of HT. Therefore, using the dosimetric advantages of IMRT, quantitative study of BMS-IMRT to reduce the toxic effects of concurrent chemoradiotherapy is a research hotspot at present.

Thrombopoietin (TPO) promotes the proliferation and survival of hematopoietic stem cells and all hematopoietic progenitor cells, accelerates the entry of stem cells into the cell cycle, and subsequently promotes the mitosis and polyploidy formation of megakaryocytes, increases the volume and number of megakaryocytes, and works with other cytokines to regulate megakaryocyte maturation. It is a commonly used drug for the treatment of thrombocytopenia in clinic.

The aim of this study is to explore the protective effect of prophylactic use of TPO on platelet inhibition in concurrent chemoradiotherapy using BMS-IMRT for esophageal cancer.

Study Type

Interventional

Enrollment (Estimated)

27

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jianyang Wang, MD
  • Phone Number: +86-13810095191
  • Email: pkucell@163.com

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100021
        • Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age greater than 18 years and less than or equal to 75 years
  • Histopathologically confirmed esophageal squamous/adenocarcinoma, clinical stage I-IV A (according to the 7th edition of AJCC（American Joint Committee on Cancer） 2010; Concurrent chemoradiotherapy (≥45Gy) was planned (regardless of whether the patient had received induction adjuvant chemotherapy).
  • Karnofsky performance status score ≥80 ·;
  • Life expectancy >6 months;
  • Meet the following laboratory diagnostic criteria:

Hemoglobin ≥120g/L, white blood cell ≥4.0×109/L, Neutrophil ≥2.0×109/L, platelet ≥100×109/L;

  • Participators had not used granulocyte colony-stimulating factor and thrombopoietin within 3 weeks before enrollment.

Exclusion Criteria:

  • A history of malignancy at other sites, excluding curable non-melanotic skin cancer and cervical carcinoma in situ;
  • Previous radiotherapy to the chest;
  • Patients with existing or suspected (thoracolumbar and pelvic) bone marrow or bone metastases, or a history of bone trauma in this region within 4 weeks;
  • Allergy to Gadolinium-based contrast agent;
  • Patients with active infection, or combined with rheumatic immune disease, long-term chronic infection, acute infection, etc., so that the body is in an inflammatory state; Blood system diseases with hematopoietic dysfunction;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: prophylactic TPO
Prophylactic TPO combined with BMS-IMRT in the esophageal cancer patients undergoing concurrent chemoradiotherapy
Drug: rhTPO

Standard treatment options:

Radiotherapy: 95% planning target volume （planning target volume，PTV） ≥45Gy(without simultaneous boost).

Concurrent chemotherapy:

Weekly regimen: paclitaxel 50mg/m2 d1, nedaplatin/cisplatin 25 mg/m2d1, a total of 5 cycles.

Three weeks regimen: paclitaxel 135-175mg/m2 d1, nedaplatin/cisplatin 80mg/m2, a total of 2 cycles.

The active bone marrow was determined by magnetic resonance（magnetic resonance，MR）, and the dose limits are: V5<95%,V10<85%,V20<60%，V30<40%；95%PTV>45Gy.

rhTPO，15000U ih. qw(during the radiotherapy course)

Other Names:
  • concurrent chemoradiotherapy
  • BMS-IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The highest grade of thrombocytopenia (CTCAE 4.0) during the radiotherapy and 1 month after the radiotherapy.
Time Frame: From start of radiotherapy and 1 month after the radiotherapy.
For esophageal cancer patients, Grade 1-4 thrombocytopenia is considered as endpoints.
From start of radiotherapy and 1 month after the radiotherapy.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Physical dosimetry of active bone marrow in BMS radiotherapy plan.
Time Frame: The first day of radiotherapy.
Low dose volume, the volume of active BM receiving 5,10,20,30 and 40 Gy
The first day of radiotherapy.
Conformity of BMS IMRT/VMAT (Volumetric Modulated Arc Therapy，VMAT) plan
Time Frame: The first day of radiotherapy.
Conformity Index (CI）was used to evaluate the conformity of IMRT/VMAT plan.
The first day of radiotherapy.
Homogeneity of IMRT/VMAT (Volumetric Modulated Arc Therapy，VMAT) plan
Time Frame: The first day of radiotherapy.
Homogeneity Index (HI) was used to evaluate the homogeneity of BMS IMRT plan.
The first day of radiotherapy.
The highest grade of leukopenia, neutropenia,anemia (CTCAE 4.0) during the radiotherapy and 1 month after the radiotherapy.
Time Frame: From start of radiotherapy and 1 month after the radiotherapy.
For esophageal cancer patients, Grade 1-4 leukopenia, neutropenia and anemia are considered as endpoints.
From start of radiotherapy and 1 month after the radiotherapy.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

JIANYANG WANG

Collaborators

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Investigators

  • Study Director: Jianyang Wang, MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 15, 2023

Primary Completion (Estimated)

May 30, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

June 2, 2023

First Submitted That Met QC Criteria

July 12, 2023

First Posted (Actual)

July 13, 2023

Study Record Updates

Last Update Posted (Actual)

July 13, 2023

Last Update Submitted That Met QC Criteria

July 12, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCC2818

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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